What is Glomerulonephritis (GN)?

What is Glomerulonephritis (GN)?

Glomerulonephritis (GN) is an umbrella term for a diverse group of autoimmune and inflammatory conditions that target the glomeruli.

These are the one million microscopic clusters of blood vessels in each kidney that act as the primary “sieves” for the blood.

Located primarily in the kidney’s outer layer (the cortex), the glomeruli filter out waste and excess water while retaining vital proteins and blood cells.

When these delicate filters are damaged by an overactive immune system, the kidneys lose their structural integrity, leading to a “leak” of nutrients and a “backup” of toxins. This can result in Acute Kidney Injury (AKI), Nephrotic Syndrome, or progressive Chronic Kidney Disease (CKD).

1. Clinical Presentation: Nephrotic vs. Nephritic Patterns

Nephrologists categorise GN into two distinct clinical patterns based on symptoms and urine chemistry.

Nephrotic Syndrome (‘Protein Leak’ Pattern)

Caused by damage to podocytes—specialised cells wrapping around the capillaries.

• Severe Oedema: Pitting swelling in the legs, hands, and around the eyes.

• Heavy Proteinuria: High protein in the urine, making it appear noticeably foamy.

• Hypoalbuminaemia: Low blood protein, reducing the blood’s ability to hold fluid in vessels.

• Hyperlipidaemia: High cholesterol as the liver overproduces lipids to compensate for protein loss.

Nephritic Syndrome (‘Blood & Pressure’ Pattern)

Caused by aggressive inflammation that ruptures the filter’s barrier.

• Haematuria: Blood in the urine (cola-colored, smoky, or microscopic).

• Oliguria: A sudden decrease in urine production.

• Hypertension: Elevated blood pressure caused by fluid retention and hormonal triggers (RAAS).

• Red Blood Cell Casts: Microscopic clumps of blood cells—a definitive sign of glomerular bleeding.

2. Classification: The 7 Primary Types of GN

Pathologists classify GN by the “injury pattern” seen under a microscope, split into Non-proliferative (structural damage) and Proliferative (highly inflammatory).

3. Advanced Diagnosis: Finding the Cause

• Urinalysis & Microscopy: Checking Albumin-to-creatinine ratios (uACR) and identifying red blood cell casts.

• Immunological Panels: Testing for “fingerprint” antibodies like PLA2R, ANA/dsDNA, ANCA, Anti-GBM, Immunoglobulins (Igs), and Complement (C3/C4) levels.

• Renal Ultrasonography: Assessing the “cortex.” A thinned cortex indicates long-term, irreversible scarring.

• Kidney Biopsy: The gold standard to identify the GN type and determine how much tissue is salvageable.

4. Modern Treatment: Protecting the Filters

• Haemodynamic Control: ACE Inhibitors/ARBs and SGLT2 Inhibitors (e.g. Dapagliflozin) reduce internal filter pressure and significantly delay the need for dialysis.

• Targeted Immunosuppression: Using Corticosteroids to dampen inflammation and “steroid-sparing” agents like Rituximab or Mycophenolate for long-term control.

• Lifestyle: Strict salt restriction and diuretics to manage fluid and blood pressure.

5. Dialysis and Transplantation

Some patients with GN progress to End-Stage Renal Failure (ESRF), despite treatment. ESRF (or kidney failure) is when the kidneys can no longer support life, and renal replacement therapy (RRT) becomes necessary.

Dialysis

• Haemodialysis: Blood is filtered through a machine, usually three times a week in a clinic.

• Peritoneal Dialysis: A fluid is put into the abdomen to filter waste through the body’s own lining.

Note: Some aggressive forms of GN (like RPGN) may require temporary dialysis while immunosuppression takes effect, allowing the kidneys to recover.

Kidney Transplantation

Transplantation is often the preferred treatment for ESRF caused by GN.

• Recurrence Risk: A key consideration in GN is the risk of the original disease returning in the new kidney. For example, FSGS and MPGN have higher recurrence rates, while others like Minimal Change are less likely to return.

• Timing: For certain types (like Anti-GBM disease), doctors wait until antibody levels are undetectable for months before proceeding with a transplant.

6. Prognosis: The Outlook

The outlook for GN has shifted from “inevitable failure” to “manageable chronic condition” for many. The biggest predictors of your outlook are:

• Proteinuria Levels: Successfully lowering protein leak to <0.5g–1g per day is the #1 predictor of avoiding dialysis.

• Tubulointerstitial Fibrosis: The amount of scarring between the filters on a biopsy. More fibrosis indicates less room for recovery.

• Response to Treatment: Patients who respond quickly to initial steroids or biological therapies generally have a much better long-term prognosis.

Summary

While Glomerulonephritis is serious, the combination of early biopsy, aggressive blood pressure targets, modern SGLT2 inhibitors and immunosuppression (in some) allows many patients to maintain stable kidney function for decades.